11 Abstracts

Additional Abstracts

• Diagnosing Multiple Sclerosis
  • Cerebral Lesions,  MRI Criteria,  Spinal Cord Lesions,
      Clinically Isolated Syndromes

• Disability Assessments
  • # 1   #2   #3   #4   # 5

• Immune System & Cells In Multiple Sclerosis
  • # 1   # 2   # 3   # 4

• MRI, MT, Diffusion, & Proton MR Spectroscopy In Multiple Sclerosis
  • #1   # 2   # 3   # 4   # 5   # 6   # 7  #8  #9  #10  #11  #12   #13   #14

• Multiple Sclerosis Lesions
  • # 1   # 2   # 3   # 4

• Axons & Disability In Multiple Sclerosis
  • #1   # 2   # 3   # 4   # 5

  • PathoGenesis Of Multiple Sclerosis
    #1   #2

  • T-Helper Cells & Cytokines In Multiple Sclerosis
    • #1   #2   # 3




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#1 ImmunoTherapy Of Multiple Sclerosis The use of Magnetic Resonance Imaging in the evaluation of clinical trials Ozawa K, Saida T Rinsho Shinkeigaku 1995 Dec;35(12):1501-3 Utano National HospitalDept of Neurology, Japan UI # 96325750 Abstract Magnetic Resonance Imaging (MRI) is being used increasingly as a measure of outcome in monitoring the efficacy of treatment for Multiple Sclerosis (MS). A major advantage of MRI is that it easily detects subclinical disease activity and thus serial MRI provides an objective and sensitive tool. In the treatment of acute attacks, CorticoSteroids are widely used to speed recovery from disability. Recently, MethylPrednisolone administered in megadose pulses was reported to reduce the conversion rate of patients with Optic Neuritis to MS. The beneficial effect of treatment was most apparent in patients with abnormal MRI scans. Among the ImmunoSuppressive or ImmunoModulatory drugs that have been used to prevent progression or reduce relapses, Interferon beta 1b is the first medication confirmed to reduce accumulations of MRI detected lesions. In a Cyclosporin treatment trial, MRI studies failed to show a significant benefit. Other therapies that require further definitive study include IntraVenous Cyclophosphamide and Oral Methotrexate or Azathioprine. A multicenter double-blind clinical trial with Mizoribine is in progress in Japan and the results will be known some time during the first half of 1997.

#2 Clinical Outcome Measures & Rating Scales In Multiple Sclerosis Trials Wingerchuk DM, Noseworthy JH, Weinshenker BG Mayo Clin Proc 1997 Nov;72(11):1070-9 Mayo Clinic, Dept of Neurology, Rochester, Minnesota 55905, USA UI # 98042417 Abstract In this review, we analyzed clinical outcome measures used in Multiple Sclerosis (MS) clinical trials in which the primary goal is to slow or arrest progression of disease. In addition, we examined rating scales that quantify Symptomatic complications of MS (for example, Spasticity) and the current role of Magnetic Resonance Imaging in MS treatment trials. Each proposed scale has advantages and deficiencies, and none meets all the criteria for an ideal outcome measure. The validity of trial design may be improved by using combinations of selected components of current scales as well as new instruments targeted to specific variables (such as motor strength). Symptom-specific rating scales are most appropriately used in trials of symptomatic therapeutic strategies for MS. Until serial Magnetic Resonance Imaging changes are definitely known to predict long-term Impairment and disability in patients with MS, clinical outcome measures will remain the primary means of assessing therapeutic efficacy in phase III clinical trials. #3 Multiple Sclerosis Use Of MRI In Evaluating New Therapies Miller DH Semin Neurol 1998;18(3):317-25 Institute of Neurology and National Hospital for Neurology and NeuroSurgery, London, UK UI # 99032474 Abstract Although definitive evaluation of new therapies should be based on clinically meaningful outcomes, there are major difficulties to overcome when conducting treatment trials with clinical endpoints such as relapse rate or progression in disability. The variable and unpredictable natural history of MS necessitates large studies (hundreds of patients) of long duration (2-3 years), with an active treatment group being compared to a control group. It is thus not surprising that there has been much effort to identify alternative laboratory markers of disease activity to monitor treatment efficacy. To be an effective replacement (or surrogate, as it is often called) of clinical outcomes the laboratory measure of disease activity needs to be objective, sensitive and cost effective, accurate, reproducible, and most importantly, predictive of clinical outcome. Magnetic Resonance Imaging (MRI) is currently the only widely used surrogate outcome. This article reviews its status as a surrogate, and proposes MRI trial designs to address specific therapeutic questions. #4 Multiple Sclerosis: What Have We Learned From MRI Studies? Khoury SJ, Weiner HL Arch Intern Med 1998 Mar 23;158(6):565-73 Brigham and Women's Hospital, Center for Neurologic Diseases, Boston, Mass 02115, USA khoury@cnd.bwh.harvard.edu UI # 98180516 Abstract We review studies that have examined the relationship between Magnetic Resonance Imaging findings and clinical disability, postmortem observations, and Cognitive dysfunction in patients with Multiple Sclerosis. We also review the use of Magnetic Resonance Imaging findings as an outcome measure in clinical trials assessing the efficacy of new therapeutic agents for the treatment of Multiple Sclerosis. More advanced applications of Magnetic Resonance Imaging and their use in Multiple Sclerosis is addressed later in the article.

#5 Clinical Scoring Methods For MS Noseworthy JH Ann Neurol 1994;36 Suppl:S80-5 Mayo Clinic, Dept of Neurology, Rochester, MN 55905 UI # 94288578 Abstract Multiple Sclerosis (MS) clinical rating scales are used to classify the degree of Neurological dysfunction and to plan treatment measures. In clinical trials, rating scales are used to monitor clinical course and response to experimental therapies. Selection of the appropriate clinical rating scale is determined by the nature of the research question (e.g., Disability, Impairment, Handicap). The Expanded Disability Status Scale (EDSS, an impairment scale) has been the most widely used clinical rating method in natural history studies and clinical trials. The EDSS has the advantage of familiarity, yet is difficult to use consistently between evaluators. In the mid and higher ranges, the EDSS is relatively insensitive to clinical changes that do not impair Gait. Evaluator unblinding may invalidate the clinical assessment of response to treatment. Additional work is needed to develop clinical and laboratory (imaging) measures of MS disease activity that will be objective, reliable, sensitive, responsive, and valid. Recent comparative studies have demonstrated that serial Magnetic Resonance Imaging (MRI) studies are 7- to 10-fold more sensitive than clinical methods in detecting subclinical evidence of apparent MS disease activity. Widespread acceptance of MRI as a primary trial outcome measure awaits the results of studies designed to determine whether MRI findings accurately reflect irreversible pathological changes and predict future disability. #6 Measurement Of Treatment Efficacy & New Trial Results In Multiple Sclerosis Noseworthy JH, Miller DH Curr Opin Neurol 1997 Jun;10(3):201-10 Mayo Clinic, Dept of Neurology, Rochester, Minnesota 55905,USA Noseworthy.john@mayo.edu UI # 97373073 Abstract The past 12 months have witnessed a considerable number of new publications of the results of phase I, II and III trials of new, putative disease modifying therapies in Multiple Sclerosis. Some important reports have appeared concerning the development and optimization of clinical and Magnetic Resonance Imaging methods for measuring therapeutic outcome. A general sense of optimism continues to exist that there will be further progress in coming years in achieving more effective strategies for treating symptoms, and for preventing relapses and disease progression. #7 Referendum on Clinical Trial Research In Multiple Sclerosis The opinion of the participants at the Jekyll Island workshop Noseworthy JH, Vandervoort MK, Hopkins M, Ebers GC Neurology 1989 Jul;39(7):977-81 Dept ofClinical Neurological Sciences, Univ of Western Ontario, London, Canada UI # 89295953 Abstract Sixty-two experienced Multiple Sclerosis (MS) investigators attending a research workshop were asked their opinions about clinical trial design, outcome measures, and treatment. Respondents favored repeated clinical observations of Neurologic function (eg, Expanded Disability Status Scale or Ambulation Index) over the opinion of a blinded physician and changes on Magnetic Resonance Imaging. There was agreement that stable MS should not be treated with ImmunoSuppressives. CorticoSteroids were rated the most effective treatment for recent disease activity. Total Lymphoid Irradiation and ImmunoSuppressives were judged more potent for the long-term management of Progressive disease. No treatment, however, received the support of more than 11% of the respondents for being of "considerable efficacy" in the long-term management of MS. Most favored a placebo-controlled design in future trials. In order to judge the acceptability of current trial design, participants were asked to act as patient surrogates and to indicate whether they would agree to participate in 4 randomized trials for which they would be eligible. The majority consented to participate in the 3 major trials currently under way, and most refused to enroll in the 1 trial that had never been initiated.

#8 MR in Monitoring the Natural History Of Multiple Sclerosis & The Effects Of Treatment Filippi M, Rovaris M, Comi G Ital J Neurol Sci 1996 Dec;17(6):385-91 Universita di Milano, Dept of Neurology, IRCCS Ospedale San Raffaele, Italy UI # 97133085 Abstract In this review the main contributions of Magnetic Resonance (MR) techniques in the monitoring of Multiple Sclerosis (MS) course, both natural or modified by treatments, are presented. MR measures well correlate with short-term disease evolution and therefore their use is appropriate as primary end-points in preliminary clinical trials evaluating the effects of new treatments. In contrast, the correlation between MR measures and long-term clinical evolution in Clinically Definite MS is less clear, thus indicating that such measures can be used at present only as a secondary end-point in large scale definitive trials. The results coming from the clinical application of newer MR techniques with higher pathological specificity are also presented and their possible future roles in monitoring treatment aimed at preventing development of disability in MS are discussed. #9 Clinical & Magnetic Resonance Imaging Predictors Of Disability in Primary & Secondary/Progressive Multiple Sclerosis Losseff NA, Kingsley DP, McDonald WI, Miller DH, Thompson AJ Mult Scler 1996 Feb;1(4):218-22 NMR Research Unit, Institute of Neurology, London, UK UI # 98005298 Abstract The role of Magnetic Resonance Imaging (MRI) in predicting disability in Multiple Sclerosis (MS) remains unclear. In this study 21 patients with Primary and Secondary/Progressive MS were reviewed 5 years following a serial MRI study of 6 months duration. In the Secondary/Progressive group (n = 11) there was a significant relationship between the occurrence of enhancing lesions and clinical relapses during the initial 6 months and increase in disability 5 years later. For both groups change in disability over the initial study period was predictive of outcome. These results suggest that the presence and frequency of Gadolinium enhancement (a marker of inflammation) and changes in disability over a short period are predictive of future deterioration in Progressive patients. #10 Magnetic Resonance Imaging In Monitoring the Treatment of Multiple Sclerosis Statistical power of parallel-groups and crossover designs Nauta JJ, Thompson AJ, Barkhof F, Miller DH J Neurol Sci 1994 Mar;122(1):6-14 Free Univ Hospital, Dept of Theory of Medicine, Biostatistics and Epidemiology, Amsterdam, The Netherlands UI # 94253836 Abstract Serial Brain Magnetic Resonance (MR) imaging detects active lesions 5-10 times more frequently than the occurrence of clinical changes in patients with early Relapsing/Remitting and Secondary Progressive Multiple Sclerosis (MS). Based on monthly unenhanced and Gadolinium enhanced MR findings in 23 unselected and untreated patients, the power of an MS treatment trial was calculated, using MR imaging activity as the primary measure of outcome. It was shown that a 80% reduction in the number of active lesions (i.e. an efficacy of 80%) should be detected using a placebo-controlled parallel-groups design with a power of 80%, if either 2 x 20 patients are scanned monthly for 4 months, or 2 x 30 patients monthly for 2 months. Short to medium term studies of new experimental treatments in MS, using MRI as the primary outcome measure, provide considerable statistical power in small patient populations studied over a short period of time. #11 The Treatment of Multiple Sclerosis Current & Future Polman CH, Hartung HP Curr Opin Neurol 1995 Jun;8(3):200-9 Free Univ Hospital, Dept of Neurology, Amsterdam, The Netherlands UI # 96023837 Abstract During the past year observations have been published that might lead to further improvement in the design of future clinical trials. At the same time, results of clinical trials have become available that suggest that a number of treatments could be of benefit in the care of patients in the various phases of Multiple Sclerosis. Future Multiple Sclerosis clinical trials should involve a blinded investigator restricted to assessing the clinical outcome variables, and because current evidence suggests that MRI gives an objective and sensitive reflection of the biological evolution of the disease, such scanning should also be included. The use of a composite outcome variable in a trial of Chronic Progressive Multiple Sclerosis should also be considered in order to increase the percentage of patients reaching the clinical endpoint. In 1994 recommendations were published for the selection of Relapsing/Remitting patients for treatment with Interferon-ß-1b. Furthermore, large and well performed clinical trials demonstrated that Interferon-ß-1a and Copolymer-1 are also partially effective, though not curative, for these patients. Two smaller studies suggested that low-dose Methotrexate and Cladribine might have a beneficial effect on the course of the disease in patients with Secondary Chronic Progressive Multiple Sclerosis, the former drug probably being less toxic. Unfortunately, therapeutic perspectives for patients with Primary/Progressive Multiple Sclerosis are less promising at present. Several studies suggest that 4-Aminopyridine and Tizanidine have therapeutic potential for symptomatic treatment; the former by improving Neurological Deficits, the latter by relieving troublesome Spasticity.

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Medical Texts

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Anatomy | Immune System | Lymphocytes | Meds
MHC | Movement | Cranial Nerves | Physiology

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Abstracts

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ANS | Bladder | Cognition | Fatigue | Fluid | Genetics
Interferons | IVIG | Nitric Oxide | Optic Neuritis | Pain
Physiology | Prions | Prognosis | ReMyelinate | Steroids
Stress | Treatments | TNF | Uric Acid | Viruses

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Updated On: 2/03/2009